Search Results (150)

Cutaneous leishmaniasis (CL) is the most common clinical form of leishmaniasis, characterized by persistent skin ulcers and nodules. Standard chemotherapeutic agents have substantial toxicity and do nothing to repair the damaged tissue, an unmet need that motivates the search for adjunctive strategies. Mesenchymal stem cells (MSCs) can modulate macrophage activity and support tissue regeneration, yet their role in CL has received limited attention. In this study, we tested whether bone marrow-derived MSCs (BM-MSCs) could attenuate Leishmania mexicana-induced inflammation and facilitate skin repair. Indirect co-culture of BM-MSCs with infected RAW264.7 macrophages shifted the macrophage phenotype from M1 toward M2, with higher IL-10 and Arg-1 expression and lower iNOS and IL-1β. In BALB/c mice with established CL, three weekly intravenous injections of BM-MSCs reduced paw swelling, improved skin histology, decreased type I collagen deposition, lowered Integrin β1 and Cytokeratin 17 expression, and reduced tissue parasite load. Immunofluorescence confirmed a predominantly M2 macrophage distribution in treated lesions. We inferred that BM-MSCs acted on both the immune and reparative aspects of the disease process, supporting their potential as an adjunct to conventional anti-leishmanial therapy. Full article

Many rhizobia use quorum sensing (QS) systems to detect their population density and modify their symbiotic behavior with the legume host. There are three LuxRI-type QS systems in Rhizobium etli CFN42, and CinR plays a key role in symbiotic performance. However, the details of how CinR regulates the symbiotic process remain unknown. In this study, we employed the RNA-Seq method to screen differentially expressed genes between the wild-type strain and the ΔcinR mutant of R. etli CFN42. We found that most of the genes related to reactive oxygen species (ROS) were expressed at lower levels in the ΔcinR mutant than in CFN42. We also found that the ΔcinR mutant was more sensitive to H₂O₂ than to CFN42. We then showed that CinR positively regulated katG expression and possessed an affinity to bind the katG promoter in the absence of the AHL ligand. The addition of AHLs promoted CinR binding to the katG promoter and enhanced katG expression. Accumulation of H₂O₂ and O₂^•− was observed in root nodules formed by the ΔcinR mutant. Crucially, katG overexpression rescued the H₂O₂-sensitive phenotype in vitro and partially restored defective symbiotic performance in nodules formed by the ΔcinR mutant on the common bean. These results suggest that CinR globally regulates ROS scavenging gene expression in order to balance oxidative stress within root nodules, promoting nitrogenase activity of R. etli CFN42. Full article

Catamenial pneumothorax is a rare form of recurrent spontaneous pneumothorax occurring in women in temporal association with the menstrual cycle, most commonly within 72 h before or after the onset of menstruation, and is frequently encountered as part of thoracic endometriosis syndrome. Thoracic endometriosis represents an extrapelvic manifestation of endometriosis in which ectopic endometrial tissue may involve the pleura, diaphragm, lung parenchyma, or airways, leading to cyclic pleuropulmonary symptoms. The clinical spectrum includes catamenial pneumothorax, catamenial hemothorax, catamenial hemoptysis, and pulmonary endometriotic nodules. This narrative review critically analyzes the diagnostic challenges and limitations of imaging modalities in thoracic endometriosis, with particular emphasis on diagnostic delay, radiological pitfalls, and the discrepancy between morphological detection and etiological confirmation. Chest radiography and computed tomography are useful for documenting acute thoracic events, whereas magnetic resonance imaging may provide additional tissue characterization in selected cases, particularly when hemorrhagic or diaphragmatic lesions are suspected. However, imaging findings are often nonspecific, temporally variable, and insufficient to establish the diagnosis when interpreted in isolation. Recognition of thoracic endometriosis therefore requires correlation of imaging findings with menstrual cyclicity, gynecological history, clinical phenotype, and, when indicated, surgical and histopathological assessment. The available evidence remains limited by retrospective designs, small case series, inconsistent diagnostic criteria, and lack of validated thoracic-specific imaging pathways. Accordingly, an integrated clinical–radiological–surgical approach should be regarded as a pragmatic diagnostic framework rather than a validated algorithm. Such an approach may improve clinical suspicion, reduce diagnostic delay, and support more appropriate multidisciplinary management of this underrecognized condition. Full article

Background/Objectives: Lipoid pneumonia (LP) is a rare and frequently underdiagnosed pulmonary condition with a broad spectrum of radiological manifestations that can closely mimic infectious, inflammatory, and neoplastic lung diseases. Despite its clinical relevance, no standardized imaging-based diagnostic pathway exists. For this reason, this pictorial narrative review aims to provide a structured, imaging-centred synthesis of LP, to characterise the full spectrum of high-resolution CT (HRCT) and magnetic resonance imaging (MRI) findings, and to propose a pragmatic diagnostic workflow. Methods: A systematic literature search was performed in PubMed, MEDLINE, Embase, and the Cochrane Library from January 1950 to February 2025. Search terms combined “lipoid pneumonia” with imaging-related keywords including “HRCT,” “computed tomography,” “MRI,” and “fat attenuation.” After screening 891 deduplicated records, 60 studies were included in the narrative synthesis. Eight illustrative institutional cases with imaging–pathology correlation were additionally selected to demonstrate key imaging phenotypes. Results: HRCT is the cornerstone modality, demonstrating intralesional fat attenuation (typically −30 to −150 HU) in 40–80% of cases depending on series and disease chronicity. Additional patterns include ground-glass opacity, crazy paving, centrilobular nodules, and mass-like consolidation mimicking malignancy. Fat attenuation is absent in up to 60% of cases when inflammatory exudate or fibrosis masks lipid content. MRI, particularly chemical shift imaging, serves as a problem-solving adjunct in pseudotumoral or densitometrically equivocal presentations. A pragmatic diagnostic workflow is proposed, integrating HRCT findings, exposure history, fat-sensitive MRI in selected cases, BAL cytology, and histopathological confirmation when required. Conclusions: A pattern-based radiological approach, anchored on HRCT and integrated with clinical exposure history, BAL cytology, and selective use of fat-sensitive MRI, enables accurate diagnosis of LP in most cases and can prevent unnecessary invasive procedures including surgical resection performed under suspicion of malignancy. Full article

Salivary adenoid cystic carcinoma (SACC) is a malignant salivary gland neoplasm characterized by aggressive local invasion and a marked propensity for metastasis. However, the role of MEOX1 in SACC progression remains poorly defined. In this study, we examined the effects of MEOX1 overexpression on the malignant behavior of SACC cells in vitro and in vivo. Human SACC-83 and SACC-LM cells were transduced with lentiviral vectors encoding MEOX1 or an empty vector control, and cell proliferation, migration, invasion, and cell cycle distribution were assessed using CCK-8, wound healing, Transwell, and flow cytometric assays, respectively. RNA sequencing was performed to characterize transcriptional changes associated with MEOX1 overexpression. In vivo, tumor growth was evaluated in BALB/c nude mice bearing subcutaneous xenografts, and pulmonary metastatic colonization was assessed using a tail vein injection model. MEOX1 overexpression reduced the proliferation, migration, and invasion of SACC cells in vitro and increased the G2/M phase fraction. In xenograft models, MEOX1-overexpressing cells formed smaller tumors and showed lower Ki67 staining than control cells. In the experimental lung metastasis model, mice injected with MEOX1-overexpressing cells developed fewer pulmonary metastatic nodules. RNA-seq identified 588 differentially expressed genes associated with MEOX1 overexpression, with enrichment in pathways including cytokine–cytokine receptor interaction, Toll-like receptor signaling, and G protein-coupled receptor signaling. Together, these findings indicate that enforced MEOX1 expression is associated with reduced malignant phenotypes in SACC models and with transcriptomic alterations in pathways related to immune response, G protein-coupled receptor signaling, and DNA damage response. Full article

The symbiotic relationship between soybean and rhizobia facilitates nodulation and nitrogen fixation, providing a sustainable nutrient supply for increasing crop yields and reducing chemical fertilizer use. However, comparative studies on the conservation and strain-specificity of host gene expression regulated by different rhizobial strains remain limited. Here, we performed a comparative analysis between the previously isolated strain, Bradyrhizobium ottawaense Bott 59, and the model strain, Bradyrhizobium diazoefficiens USDA 110. Symbiotic phenotypes were evaluated after inoculation, and a root transcriptomic analysis was conducted at 3 dpi to assess early molecular responses. At 21 dpi, Bott 59-inoculated plants outperformed plants inoculated with USDA 110 in nodule number, nitrogenase activity, and biomass. Transcriptomic analysis revealed conserved host responses to both rhizobial strains, including NIN-mediated signaling, AON signaling, and the biosynthesis of phenylpropanoids and brassinosteroids. Further analysis revealed that Bott 59 specifically induced the expression of genes involved in isoflavonoid and flavonoid biosynthesis, including those encoding I2H, and HI4OMT. Moreover, Bott 59 triggered more pronounced transcriptional reprogramming in auxin, cytokinin, and jasmonic acid signaling pathways, along with differential expression of a broader set of transcription factor genes. Collectively, this study systematically unravels the conserved and strain-specific transcriptional regulatory events underlying host–rhizobium interactions. Our findings provide valuable theoretical insights and transcriptomic resources for further dissecting the molecular mechanisms of symbiotic nitrogen fixation (SNF), as well as for the targeted genetic improvement of crop nodulation and nitrogen fixation efficiency. Full article

Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis characterized by recurrent nodules, abscesses, and sinus tract formation in intertriginous skin. Although HS is increasingly recognized as an autoinflammatory condition rather than a classical infection, antimicrobial therapies remain central to disease management, implicating a potential role for the cutaneous microbiome in disease activity. Recent advances in culture-independent sequencing techniques have enabled more detailed characterization of microbial communities in HS, revealing consistent alterations in microbial composition and diversity. Compared with healthy skin, HS lesions exhibit reduced microbial diversity, depletion of commensal organisms such as Cutibacterium acnes, and enrichment of anaerobic bacteria including Prevotella, Porphyromonas, and Finegoldia. These alterations are more pronounced in chronic, tunnel-forming disease and are frequently associated with biofilm formation, which may contribute to treatment resistance and persistent inflammation. Microbiome changes have also been observed beyond overtly lesional skin, suggesting a broader field effect. Evidence regarding extracutaneous microbial compartments, particularly the gut microbiome, remains limited and heterogeneous, while methodological variability in sampling, sequencing, and treatment exposure continues to complicate cross-study comparisons. Emerging data further suggest that immune-targeted therapies, including biologic and small-molecule agents, may indirectly influence microbial community structure through modulation of the inflammatory milieu. Collectively, the available evidence supports cutaneous dysbiosis as a characteristic feature of HS that may potentially interact bidirectionally with immune dysfunction. Future longitudinal, multi-omic studies integrated with clinical phenotyping will be critical to clarify causal relationships and to determine whether microbiome modulation can be leveraged to improve therapeutic outcomes in HS. Full article

Growing evidence indicates that myocardial infarction (MI) is the clinical manifestation of heterogeneous plaque substrates with distinct molecular, cellular, and biomechanical mechanisms. Acute coronary thrombosis (ACT) most commonly arises from plaque rupture (PR), plaque erosion (PE), and calcified nodules (CNs), each associated with different inflammatory profiles, thrombus composition, clinical presentation, and prognosis. This comprehensive review provides a clinician-oriented synthesis of the pathophysiological mechanisms underlying these three principal plaque phenotypes and discusses their implications for the contemporary management of acute coronary syndromes (ACS). We examine the molecular and cellular determinants of plaque instability and highlight how systemic factors such as plaque burden, impaired healing responses, and myocardial jeopardy modulate clinical risk. The role of intracoronary and non-invasive imaging is discussed primarily as a tool to elucidate plaque biology with direct clinical relevance rather than merely as a procedural guide. Building on these insights, we propose a conceptual framework for integrating plaque biology into clinical decision-making across the acute phase, secondary prevention, and long-term follow-up. In particular, recognizing the biological heterogeneity of plaque substrates may support more personalized therapeutic strategies, enabling clinicians to tailor pharmacological and interventional approaches according to the underlying plaque phenotype and patient-specific risk profile. Finally, we briefly address emerging perspectives, including the potential role of artificial intelligence (AI) in refining plaque characterization, risk stratification, and precision cardiovascular prevention. Overall, recognition of PR, PE, and CNs as biologically distinct entities supports a shift toward mechanism-informed and personalized management of MI, aligning advances in plaque biology with the principles of precision cardiovascular medicine. Full article

Background: Extracranial metastasis (EM) from glioblastoma (GB), IDH-wildtype (WHO CNS 2021 grade 4) is rare and often under-recognized, yet it has immediate implications for staging and management. We report a case series integrating advanced neuroimaging, whole-body imaging, and pathology/biomarkers to characterize imaging–pathology correlates of EM and highlight practical clinical triggers that should prompt systemic evaluation. Case presentation: We report three patients with adult-type, IDH-wildtype GB who developed EM confirmed by cytology/histology and/or concordant multimodality imaging. Brain MRI (1.5T/3T) demonstrated aggressive primary tumors with qualitative elevation of DSC-perfusion and frequent tumor–surface contact (dural, ependymal/leptomeningeal contact). Intratumoral susceptibility signal reached grade 3 where assessed. All patients underwent surgical resection followed by temozolomide-based chemoradiation; two received fotemustine and bevacizumab, and one underwent re-irradiation. EM presented with clinical triggers including severe axial/back pain, palpable cervical masses, and/or cytopenias. Initial EM sites were bone marrow/vertebrae (n = 1) and cervical lymph nodes (n = 2); staging revealed additional osseous disease in both nodal cases and a small pulmonary nodule in one. Nodal and osseous lesions were FDG-avid on 18F-FDG PET/CT. OLIG2-positive cytology confirmed cervical nodal metastases, and bone marrow aspiration with GFAP/OLIG2 positivity confirmed medullary infiltration. All tumors shared a molecular profile of TERT-promoter mutation, ATRX wild-type, TP53 mutation, and MGMT-promoter methylation. Despite attempts at second- and third-line therapies, disease progression was rapid, and all patients succumbed within 8–16 months of diagnosis. Discussion: This series underscores that EM can occur despite MGMT-promoter methylation and supports the concept of heterogeneous metastatic phenotypes in GB. Our cases reinforce that new axial/back pain or hematologic abnormalities may signal osseous or marrow involvement, and necrotic cervical lymphadenopathy in GB patients warrants dedicated imaging and tissue confirmation with glial markers. Integrating brain MRI features (high perfusion, surface contact, susceptibility burden) with FDG-PET/CT and targeted cytology/pathology can expedite diagnosis and inform multidisciplinary care. Conclusions: EM can arise despite MGMT-promoter methylation in IDH-wildtype GBM. Imaging red flags (high perfusion, surface contact, necrotic/FDG-avid cervical nodes) and clinical cues (axial pain, cytopenias, neck masses) should prompt early systemic staging (CT/PET-CT) and targeted tissue confirmation to advance management. Full article

Background and Clinical Significance: Modern neuro-oncologists encounter a major challenge when dealing with glioblastomas located in the dominant hemisphere’s temporo-basal area, because their invasive nature disrupts the proximity to eloquent cortical areas (language and speech), as well as skull base venous structures, which can lead to a quick decline in function from the disruptions in these networks and the disconnection of corridor-level pathways. This manuscript illustrates the application of metric-based phenotyping, anatomically defined imaging, and venous-anchored microsurgical techniques that can aid in preserving the remaining functional reserve in patients with dominant hemisphere glioblastomas and demonstrate measurable outcomes through longitudinal follow-up data. Case Presentation: A 48-year-old right-handed male patient presented with a four-week history of progressively worsening symptoms consistent with a dominant hemisphere syndrome, resulting in a significant decrease in his independence (mRS 0 → 4; BI 55/100; IADL 2/8). His symptoms included non-fluent expressive aphasia with a marked inability to generate words and respond to verbal cues (BNT 8/30; SF 4 WPM). Additionally, he experienced prolonged lateralizing hemisensory decompensation and corticospinal tract dysfunction. Imaging studies revealed a large multiloculated cystic lesion located in the left temporo-basal region. The lesion displayed a thick irregular peripheral enhancement pattern with mural nodules and septa, and surrounding T2 hyperintensity extending into the temporal associative white matter, indicating disruption of the lexical–semantic networks and corridor-level tracts. Utilizing continuous SSEPS/MEPs during surgery, a skull base parallel ventral temporal corridor was developed to allow decompression of the cyst first, followed by cyst evacuation, inside-out cytoreduction, subpial dissection, and specific preservation of both superficial and deep temporal veins using selective capsular preservation at venous interface locations where necessary. Postoperative CT scans performed on POD #3 and POD #7 indicated stable decompression without hemorrhage or hydrocephalus complications, followed by rapid quantitative improvement in NIHSS (8 → 2), MoCA (18 → 26), BNT (8 → 26), SF (4 → 12), mRS (2 at discharge, 1 at follow-up), BI (85 at discharge, 95 at follow-up), and IADL (6/8 at discharge, 8/8 at follow-up). Histopathological examination confirmed a diagnosis of glioblastoma. Conclusions: This case study supports a model of a network- and vein-constrained glioblastoma of the dominant hemisphere in the temporo-basal region that can result in substantial restoration of language capabilities and preservation of functional reserves for additional therapies using venous-anchored subpial microsurgical approaches. The use of objective and quantifiable measures of phenotyping and longitudinal follow-up tracking could provide a reproducible method for measuring the degree of recovery of the affected network(s) and establishing safe boundaries for temporal glioma surgery. Full article

Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical challenge, driven in part by resistance–nodulation–division (RND) efflux pumps that reduce intracellular antibiotic concentrations and limit the efficacy of many antibacterial agents, including fluoroquinolones. The aim of this study was to identify and characterize TXA11114 as a small-molecule efflux pump inhibitor (EPI) capable of restoring the activity of the fluoroquinolone levofloxacin against MDR P. aeruginosa. Methods: The antibacterial activity of the TXA11114–levofloxacin combination was evaluated using minimum inhibitory concentration (MIC) assays against panels of clinical isolates. Mechanistic studies included levofloxacin accumulation assays, ethidium bromide accumulation assays, outer-membrane permeability measurements, and whole-genome sequencing of mutants with altered potentiation phenotypes. In vivo efficacy was evaluated in murine thigh and lung infection models, while preliminary safety and drug-like properties were assessed using cytotoxicity assays and in vitro ADME profiling. Results: The TXA11114–levofloxacin combination produced > 1 log₁₀ CFU reductions in bacterial burden in murine thigh and lung infection models, exceeding the activity of levofloxacin monotherapy. TXA11114 markedly potentiated levofloxacin activity, producing substantial reductions in levofloxacin MIC values across multiple MDR clinical isolates, and also enhanced the activity of several additional efflux pump substrates, including β-lactams, tetracyclines, chloramphenicol, and trimethoprim–sulfamethoxazole. Mechanistic experiments demonstrated increased intracellular accumulation of efflux substrates without evidence of nonspecific membrane disruption, and mutations in ompH were associated with altered potentiation phenotypes. Conclusions: The TXA11114–levofloxacin combination produced significantly greater bacterial reductions than levofloxacin monotherapy in murine infection models. Levofloxacin was selected because fluoroquinolone resistance in P. aeruginosa is frequently driven by efflux-mediated mechanisms. While this study focused on levofloxacin potentiation, future work will evaluate additional efflux pump substrates and further define the molecular target of TXA11114. Full article

The large yellow croaker (Larimichthys crocea) is a key mariculture species in China, however, its industry is threatened by visceral white nodules disease (VWND) caused by the bacterium Pseudomonas plecoglossicida. A significant challenge in breeding is the potential genetic trade-off between growth and disease resistance. To investigate their genetic relationship, we constructed a high-density SNP-based genetic linkage map for L. crocea using a F1 full-sib family (n = 150). The map comprised 24 linkage groups with 32,429 bin markers and an average interval of 0.051 cM. Based on this map, we conducted QTL mapping for one yield trait (body weight), eight morphological traits, and three VWND-resistance traits (survival time, AT; spleen and liver pathogen loads). Phenotypic analysis revealed strong integration among growth traits and a moderate positive correlation between growth traits and AT. QTL mapping identified 53 QTLs for growth (PVE = 0.14–5.83%) and 20 for resistance (PVE = 0.78–8.93%). Notably, only two genomic intervals exhibited co-localization between a morphological trait (AL or BL) and AT, each explaining a modest phenotypic variance (0.66–5.99%). The largest-effect QTLs for growth and resistance were mapped to distinct linkage groups, and candidate genes within the co-localized intervals (Unc5d, SCN5A, HUS1) are involved in fundamental cellular processes rather than core growth or immune pathways. These results suggest that yield, morphological, and VWND-resistance traits in L. crocea are largely under independent genetic control within the studied family, indicating that simultaneous improvement of growth and disease resistance is feasible. This study provides a molecular basis for breeding strategies aimed at overcoming the trait trade-off bottleneck in this economically vital species. Full article

Different rhizobial strains can lead to distinct symbiotic phenotypes in alfalfa, yet molecular differences at the mature nodule stage remain unclear. Here, we analyzed 21-day post-inoculation (dpi) nodules induced by strains WE2 and WWL2. We measured nitrogenase activity (acetylene reduction assay, ARA) and performed dual RNA-seq to compare gene expression in both the alfalfa host and the rhizobia. On the host side, WE2-induced nodules showed higher expression of mature nodule marker genes (ENOD93 and leghemoglobin (Lb) genes) and higher expression of genes encoding SWEET transporters and amino acid and peptide transporters. Host differentially expressed genes were enriched in pathways related to transmembrane transport, redox and heme-related functions, and processes linked to maintaining microaerobic conditions. On the rhizobial side, WE2 nodules showed higher expression of genes involved in microaerobic respiration and nitrogen fixation (e.g., nif/fix and key respiratory chain genes), whereas WWL2 nodules showed higher expression of genes linked to transport, chemotaxis/motility, and environmental information processing. Together, these host and rhizobia expression patterns suggest coordinated differences between host pathways related to resource supply and microaerobic conditions and rhizobial expression programs for respiration and nitrogen fixation. Based on these associations, we propose a working model and provide candidate genes and pathways for functional validation and inoculant screening. Full article

Dissecting cellulitis of the scalp (DCS) is a chronic, inflammatory follicular occlusion disorder characterized by painful nodules, abscesses, and sinus tracts that lead to scarring alopecia. The therapeutic goal is to limit disease progression and the extent of scarring. Although DCS is traditionally managed with systemic retinoids, antibiotics, and surgical interventions, therapeutic responses are variable and long-term remission remains challenging. Recent insights into the immunological overlap between DCS, hidradenitis suppurativa (HS), and other autoinflammatory follicular disorders have expanded therapeutic options, particularly with biologic agents targeting tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and IL-23 pathways, as well as Janus kinase (JAK) inhibitors. This review synthesizes the current evidence on medical, procedural, and emerging targeted therapies for DCS, incorporating data from case reports, case series, retrospective cohorts, and recent systematic reviews up to 2025. Special emphasis is placed on the evolving role of biologics and small-molecule inhibitors, which show growing promise for refractory or syndromic presentations. Current evidence supports a stepwise, phenotype-driven approach in which systemic retinoids remain first-line systemic therapy, while biologics represent a rational and increasingly evidence-supported option for moderate-to-severe, treatment-resistant, or syndromic disease. Further controlled studies are needed to define optimal sequencing, duration, and combination strategies for long-term management. Full article

Inflammatory mammary carcinoma (IMC) is an aggressive mammary carcinoma phenotype characterized by tumor emboli within superficial dermal lymphatic vessels and early metastasis. A captive Bengal tiger (Panthera tigris tigris) presented with large abdominal mammary masses and regional lymphadenopathy; contrast-enhanced computed tomography also revealed a pulmonary nodule. Postmortem examination and histopathology confirmed mammary carcinoma with dermal lymphatic tumor emboli and metastases to regional lymph nodes and the lung. Tumor emboli were cytokeratin positive, supporting epithelial origin and an IMC diagnosis, and neoplastic cells were immunopositive for cytokeratin with concurrent vimentin immunoreactivity. This case highlights the clinicopathologic basis of IMC and the diagnostic importance of including full-thickness skin and adjacent subcutis in the sampling plan. Full article